Abstract
Diesel exhaust particles are priority pollutants in the environment due to their carcinogenicity and mutagenicity. 1-Nitropyrene (1-NP), a typical diesel exhaust nitro-polycyclic aromatic hydrocarbon, was defined as a possible carcinogenic factor by the International Agency for Research on Cancer. However, there is insufficient information about cancer hematogenous metastasis induced by 1-NP, and there is an urgent need to determine the oncogenic signaling pathway of 1-NP. Our study revealed the stronger carcinogenic effect of 1-NP on endothelial cell adhesion and lung cancer metastasis through in vivo and in vitro experiments. Specifically, 1-NP induces the inactivation of serine/threonine kinase (MST1/2) and large tumor suppressor (LATS1/2), resulting in the dephosphorylation and nuclear translocation of Yes-associated protein (YAP). Then, the YAP/TEAD (TEA domain transcription factor) interaction profoundly increases the level of transcription of endothelial adhesion genes (E-selectin) related to cance...
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